The circadian system is responsible for coordinating biological processes of various tissues in the body and perturbations of this system have been shown to cause disease. Circadian regulation of cardiovascular activity provides temporal structure to anticipate metabolic demands of the body however the mechanism by which the Suprachiasmatic Nucleus (SCN), the master clock driving circadian rhythms, communicates with the heart is unclear. We propose that the SCN communicates circadian signals to the heart via the autonomic nervous system (ANS). The neuropeptide, Vasoactive Intestinal Peptide (VIP), is expressed in the SCN and is implicated in coordinating cellular oscillators. VIP is also found in the ANS circuitry to the heart and secreted by the PNS. Therefore, VIP could be mediating circadian information by synchronizing the phase of the molecular clock in cardiomyocytes. We will explore the role of VIP in mediating circadian information, by measuring rhythms of HR and gene expression in cardiomyocytes and assessing autonomic activity in VIP- deficient mice. We will also determine whether temporally structured exercise can rescue circadian rhythms of HR and gene expression in the hearts of VIP-deficient mice. Lastly, we will also look at the possible role of VIP in the synchronization of circadian rhythms in cardiomyocytes in culture. These studies will determine the contribution of VIP in the circadian regulation of heart function and the molecular clock in cardiomyocytes. PUBLIC HEALTH RELEVANCE: By developing a mechanistic-based understanding of how circadian system regulates cardiovascular function, we hope to be able to develop new therapies and disease management strategies that can be applied to a range of psychiatric and neurological disorders. This understanding also has broad implications for understanding temporal organization of human performance.